scholarly journals The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes

2019 ◽  
Author(s):  
Yehonatan Alcalay ◽  
Silke Fuchs ◽  
Roberto Galizi ◽  
Federica Bernardini ◽  
Roya Elaine Haghighat-Khah ◽  
...  
Keyword(s):  
Sex Ratio ◽  
Y Chromosome ◽  
X Chromosome ◽  
Sex Chromosome ◽  
Unexpected Event ◽  
Meiotic Sex Chromosome Inactivation ◽  
Ratio Distortion ◽  
High Fraction ◽  
Malaria Mosquitoes ◽  
Population Suppression

AbstractSynthetic sex-ratio distorters based on X-chromosome shredding are predicted to be more efficient than sterile males for population suppression of malaria mosquitoes using genetic control. X-chromosome shredding operates through the targeted elimination of X-chromosome-bearing gametes during male spermatogenesis, resulting in males that have a high fraction of male offspring. Strains harboring autosomal constructs containing a modified endonuclease I-PpoI have now been developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion towards males. Data are being gathered for these strains for submission of regulatory dossiers for contained use and subsequent field release in West Africa. Since autosomal X-shredders are transmitted in a Mendelian fashion and can be selected against their frequency in the population is expected to decline once releases are halted. However, any unintended transfer of the X-shredder to the Y-chromosome could theoretically change these dynamics: This could lead to 100% transmission of the newly Y-linked X-shredder to the predominant male-biased offspring and its insulation from negative selection in females, resulting in its potential spread in the population and ultimately to suppression. Here, we analyze plausible mechanisms whereby an autosomal X-shredder could become linked to the Y-chromosome after release and provide data regarding its potential for activity should it become linked to the Y-chromosome. Our results strongly suggest that Y-chromosome linkage through remobilization of the transposon used for the initial genetic transformation is unlikely, and that, in the unexpected event that the X-shredder becomes linked to the Y-chromosome, expression and activity of the X-shredder would likely be inhibited by meiotic sex chromosome inactivation. We conclude that a functioning X-shredding-based Y-drive resulting from a naturally induced transposition or translocation of the transgene onto the Y-chromosome is unlikely.

scholarly journals The Potential for a Released Autosomal X-Shredder Becoming a Driving-Y Chromosome and Invasively Suppressing Wild Populations of Malaria Mosquitoes

2021 ◽  
Vol 9 ◽  
Author(s):  
Yehonatan Alcalay ◽  
Silke Fuchs ◽  
Roberto Galizi ◽  
Federica Bernardini ◽  
Roya Elaine Haghighat-Khah ◽  
...  
Keyword(s):  
Sex Ratio ◽  
Y Chromosome ◽  
Population Declines ◽  
Wild Type ◽  
Ratio Distortion ◽  
The Stability ◽  
Malaria Mosquitoes ◽  
Population Suppression ◽  
Sex Ratio Distortion ◽  
Sterile Male Releases

Sex-ratio distorters based on X-chromosome shredding are more efficient than sterile male releases for population suppression. X-shredding is a form of sex distortion that skews spermatogenesis of XY males towards the preferential transmission of Y-bearing gametes, resulting in a higher fraction of sons than daughters. Strains harboring X-shredders on autosomes were first developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion. Since autosomal X-shredders are transmitted in a Mendelian fashion and can be selected against, their frequency in the population declines once releases are halted. However, unintended transfer of X-shredders to the Y-chromosome could produce an invasive meiotic drive element, that benefits from its biased transmission to the predominant male-biased offspring and its effective shielding from female negative selection. Indeed, linkage to the Y-chromosome of an active X-shredder instigated the development of the nuclease-based X-shredding system. Here, we analyze mechanisms whereby an autosomal X-shredder could become unintentionally Y-linked after release by evaluating the stability of an established X-shredder strain that is being considered for release, exploring its potential for remobilization in laboratory and wild-type genomes of An. gambiae and provide data regarding expression on the mosquito Y-chromosome. Our data suggest that an invasive X-shredder resulting from a post-release movement of such autosomal transgenes onto the Y-chromosome is unlikely.

scholarly journals Modifier Genes of the Sex Ratio Trait in Drosophila pseudoobscura

Genetics ◽  
1987 ◽  
Vol 116 (2) ◽  
pp. 275-283
Author(s):  
Gary Cobbs
Keyword(s):  
Sex Ratio ◽  
Y Chromosome ◽  
X Chromosome ◽  
High Frequency ◽  
Sex Chromosome ◽  
Drosophila Pseudoobscura ◽  
Sterile Male ◽  
Very High Frequency ◽  
Very High ◽  
Chromosome Nondisjunction

ABSTRACT The msr trait of Drosophila pseudoobscura occurs when "sex-ratio" males produce a very high frequency of null-X sperm which give rise to sterile male (X/O) progeny. The trait involves dramatically lowered fecundity due to spermiogenic failure. The msr trait is multigenic and the genes are located on autosomes II, III and IV of the L116 laboratory stock. This stock also carries genes on the Y chromosome that lower the level of msr. When the genes on the L116 autosomes are present together or with those on the Y chromosome of other stocks, they interact cooperatively to produce very high levels of msr. The msr genes require the presence of a sex-ratio X chromosome to have any effect and thus may be regarded as modifiers of the "sex-ratio" phenotype. Crosses show that the genes causing msr are primarily recessive but have some expression when heterozygous. Sex chromosome nondisjunction is proposed as the mechanism underlying the msr trait.

scholarly journals EXPERIMENTAL POPULATION GENETICS OF MEIOTIC DRIVE SYSTEMS. III. NEUTRALIZATION OF SEX-RATIO DISTORTION IN DROSOPHILA THROUGH SEX-CHROMOSOME ANEUPLOIDY

Genetics ◽  
1981 ◽  
Vol 98 (2) ◽  
pp. 317-334
Author(s):  
Terrence W Lyttle
Keyword(s):  
Sex Ratio ◽  
Y Chromosome ◽  
Sex Chromosome ◽  
Meiotic Drive ◽  
Generation Model ◽  
Sex Chromosome Aneuploidy ◽  
Population Extinction ◽  
Chromosome Aneuploidy ◽  
Ratio Distortion ◽  
Sex Ratio Distortion

ABSTRACT Laboratory populations of Drosophila melanogaster were challenged by pseudo-Y drive, which mimics true Y-chromosome meiotic drive through the incorporation of Segregation Distorter (SD) in a T(Y;2) complex. This causes extreme sex-ratio distrotion and can ultimately lead to population extinction. Populations normally respond by the gradual accumulation of drive suppressors, and this reduction in strength of distortion allows the sex ratio to move closer to the optimal value of 1:1. One population monitored, however, was rapidly able to neutralize the effects of sex-ratio distortion by the accumulation of sex-chromosome aneuploids (XXY, XYY). This apparently occurs because XX-bearing eggs, produced in relatively high numbers (~4%) by XXY genotypes, become the main population source of females under strong Y-chromosome drive. Computer simulation for a discrete generation model incorporating random mating with differences in fitness and segregation permits several predictions that can be compared to the data. First, sex-chromosome aneuploids should rapidly attain equilibrium, while stabilizing the population at ~60% males. This sex ratio should be roughly independent of the strength of the meiotic drive. Moreover, conditions favoring the accumulation of drive suppressors (e.g., weak distortion, slow population extinction) are insufficient for maintaining aneuploidy, while conditions favoring aneuploidy (e.g., strong distortion, low production of females) lead to population extinction before drive suppressors can accumulate. Thus, the different mechanisms for neutralizing sex-ratio distortion are complementary. In addition, Y drive and sex-chromosome aneuploidy are potentially co-adaptive, since under some conditions neither will survive alone. Finally, these results suggest the possibility that genetic variants promoting sex-chromosome nondisjunction may have a selective advantage in natural populations faced with sex-ratio distortion.

scholarly journals Sex Chromosome Meiotic Drive in Stalk-Eyed Flies

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1169-1180 ◽  
Author(s):  
Daven C Presgraves ◽  
Emily Severance ◽  
Gerald S Willrinson
Keyword(s):  
Sex Ratio ◽  
Sex Chromosome ◽  
Sex Ratios ◽  
Natural Populations ◽  
Meiotic Drive ◽  
Operational Sex Ratio ◽  
Genetic Modifiers ◽  
Ratio Distortion ◽  
The Impact ◽  
Sex Ratio Distortion

Meiotically driven sex chromosomes can quickly spread to fixation and cause population extinction unless balanced by selection or suppressed by genetic modifiers. We report results of genetic analyses that demonstrate that extreme female-biased sex ratios in two sister species of stalk-eyed flies, Cyrtodiopsis dalmanni and C. whitei, are due to a meiotic drive element on the X chromosome (Xd). Relatively high frequencies of Xd in C. dalmanni and C. whitei (13–17% and 29%, respectively) cause female-biased sex ratios in natural populations of both species. Sex ratio distortion is associated with spermatid degeneration in male carriers of Xd. Variation in sex ratios is caused by Y-linked and autosomal factors that decrease the intensity of meiotic drive. Y-linked polymorphism for resistance to drive exists in C. dalmanni in which a resistant Y chromosome reduces the intensity and reverses the direction of meiotic drive. When paired with Xd, modifying Y chromosomes (Ym) cause the transmission of predominantly Y-bearing sperm, and on average, production of 63% male progeny. The absence of sex ratio distortion in closely related monomorphic outgroup species suggests that this meiotic drive system may predate the origin of C. whitei and C. dalmanni. We discuss factors likely to be involved in the persistence of these sex-linked polymorphisms and consider the impact of Xd on the operational sex ratio and the intensity of sexual selection in these extremely sexually dimorphic flies.

Sperm Competition and the Dynamics of X Chromosome Drive: Stability and Extinction

Genetics ◽  
2002 ◽  
Vol 160 (4) ◽  
pp. 1721-1731 ◽  
Author(s):  
Jesse E Taylor ◽  
John Jaenike
Keyword(s):  
Sex Ratio ◽  
Sperm Competition ◽  
X Chromosome ◽  
Sex Chromosome ◽  
Basin Of Attraction ◽  
Male Mating ◽  
Male And Female ◽  
Mating Rate ◽  
Female Mating ◽  
Balanced Polymorphism

AbstractSeveral empirical studies of sperm competition in populations polymorphic for a driving X chromosome have revealed that Sex-ratio males (those carrying a driving X) are at a disadvantage relative to Standard males. Because the frequency of the driving X chromosome determines the population-level sex ratio and thus alters male and female mating rates, the evolutionary consequences of sperm competition for sex chromosome meiotic drive are subtle. As the SR allele increases in frequency, the ratio of females to males also increases, causing an increase in the male mating rate and a decrease in the female mating rate. While the former change may exacerbate the disadvantage of Sex-ratio males during sperm competition, the latter change decreases the incidence of sperm competition within the population. We analyze a model of the effects of sperm competition on a driving X chromosome and show that these opposing trends in male and female mating rates can result in two coexisting locally stable equilibria, one corresponding to a balanced polymorphism of the SR and ST alleles and the second to fixation of the ST allele. Stochastic fluctuations of either the population sex ratio or the SR frequency can then drive the population away from the balanced polymorphism and into the basin of attraction for the second equilibrium, resulting in fixation of the SR allele and extinction of the population.

scholarly journals A second X chromosome contributes to resilience in a mouse model of Alzheimer’s disease

2020 ◽  
Vol 12 (558) ◽  
pp. eaaz5677 ◽  
Author(s):  
Emily J. Davis ◽  
Lauren Broestl ◽  
Samira Abdulai-Saiku ◽  
Kurtresha Worden ◽  
Luke W. Bonham ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Y Chromosome ◽  
X Chromosome ◽  
Sex Chromosome ◽  
Testicular Development ◽  
X Chromosomes ◽  
Model Of Alzheimer’S Disease ◽  
Preclinical Ad ◽  
Brain Expression

A major sex difference in Alzheimer’s disease (AD) is that men with the disease die earlier than do women. In aging and preclinical AD, men also show more cognitive deficits. Here, we show that the X chromosome affects AD-related vulnerability in mice expressing the human amyloid precursor protein (hAPP), a model of AD. XY-hAPP mice genetically modified to develop testicles or ovaries showed worse mortality and deficits than did XX-hAPP mice with either gonad, indicating a sex chromosome effect. To dissect whether the absence of a second X chromosome or the presence of a Y chromosome conferred a disadvantage on male mice, we varied sex chromosome dosage. With or without a Y chromosome, hAPP mice with one X chromosome showed worse mortality and deficits than did those with two X chromosomes. Thus, adding a second X chromosome conferred resilience to XY males and XO females. In addition, the Y chromosome, its sex-determining region Y gene (Sry), or testicular development modified mortality in hAPP mice with one X chromosome such that XY males with testicles survived longer than did XY or XO females with ovaries. Furthermore, a second X chromosome conferred resilience potentially through the candidate gene Kdm6a, which does not undergo X-linked inactivation. In humans, genetic variation in KDM6A was linked to higher brain expression and associated with less cognitive decline in aging and preclinical AD, suggesting its relevance to human brain health. Our study suggests a potential role for sex chromosomes in modulating disease vulnerability related to AD.

Photographic polytene chromosome maps for Glossina morsitans submorsitans (Diptera: Glossinidae): cytogenetic analysis of a colony with sex-ratio distortion

Genome ◽  
2002 ◽  
Vol 45 (5) ◽  
pp. 871-880 ◽  
Author(s):  
A Gariou-Papalexiou ◽  
G Yannopoulos ◽  
A Zacharopoulou ◽  
R H Gooding
Keyword(s):  
Sex Ratio ◽  
Polytene Chromosome ◽  
X Chromosome ◽  
Polytene Chromosomes ◽  
Glossina Morsitans ◽  
Glossina Morsitans Submorsitans ◽  
Ratio Distortion ◽  
Chromosome Maps ◽  
Sex Ratio Distortion ◽  
Pharate Adult

Photographic polytene chromosome maps from trichogen cells of pharate adult Glossina morsitans submorsitans were constructed. Using the standard system employed to map polytene chromosomes of Drosophila, the characteristic landmarks were described for the X chromosome and the two autosomes (L1 and L2). Sex-ratio distortion, which is expressed in male G. m. submorsitans, was found to be associated with an X chromosome (XB) that contains three inversions in each arm. Preliminary data indicate no differences in the fecundity of XAXA and XAXB females, but there are indications that G. m. submorsitans in colonies originating from Burkina Faso and Nigeria have genes on the autosomes and (or) the Y chromosome that suppress expression of sex-ratio distortion.Key words: tsetse, Glossina morsitans submorsitans, polytene chromosome maps, inversions, sex-ratio distortion.

Variation in Y chromosome meiotic drive in Aedes aegypti (Diptera: Culicidae): a potential genetic approach to mosquito control

1997 ◽  
Vol 87 (6) ◽  
pp. 617-623 ◽  
Author(s):  
K. O. Owusu-Daaku ◽  
R. J. Wood ◽  
R. D. Butler
Keyword(s):  
Sex Ratio ◽  
Aedes Aegypti ◽  
Y Chromosome ◽  
Reciprocal Cross ◽  
Mosquito Control ◽  
Meiotic Drive ◽  
Genetic Approach ◽  
Single Form ◽  
Ratio Distortion ◽  
Sex Ratio Distortion

AbstractReciprocal crosses between strains of Aedes aegypti (Linnaeus) from different geographical areas have revealed an unexpectedly complex pattern of holandrically inherited male biased sex ratios in F2. The variation has been interpreted in terms of a web of X–Y interactions in Fl, in which the Y chromosome may or may not show meiotic drive against the X chromosome with which it is paired. The pattern of inheritance is not in agreement with a single form of Y chromosome, driving with different degrees of intensity against Xs of different sensitivity, but indicates different forms of driving Y chromosome. A rule has emerged that if Fl males from any cross give rise to a male distorted sex ratio in their progeny (F2), the males from the reciprocal cross give rise to a normal sex ratio. All eleven newly colonized strains from Ghana showed Y meiotic drive against the Xs of five strains, one of American and four of Australian origin, although one of the eleven showed a greater degree of drive than the other ten against the same sensitive strains. The variation observed is discussed in relation to previous studies on meiotic drive by the MD haplotype, and to the possible exploitation of sex ratio distortion in controlling this potentially dangerous insect.

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